膀胱癌及其癌旁组织gp-96结合肽库的初步探讨
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摘要
目的热休克蛋白gp96作为分子伴侣,能够与肿瘤抗原肽形成gp96—肽复合物,参与肿瘤抗原向MHC-I类分子途径的递呈过程,从而激活CD8+T淋巴细胞,产生抗肿瘤特异性免疫应答。因此,gp96—肽复合物疫苗为肿瘤的免疫治疗提供了新的思路。传统制备gp96的方法虽然已经成熟,但是由于组织来源的限制以及纯化工序过于繁杂,难以进行工业化生产。因此寻找一种快速有效而又高度特异性的方法纯化gp96,成为该疫苗大规模临床应用所要解决的首要问题。研究进一步证实,在gp96—肽复合物中起肿瘤免疫作用的是抗原肽,不是gp96自身,gp96结合的多肽才是疫苗制备和诱导特异性免疫应答的分子基础。因此,对gp96结合肽库的鉴定和分析,成为构建gp96—肽复合物疫苗、探讨相关作用机理及疫苗人工化生产等急待解决的问题。
方法用固相化的gp96蛋白从人天然噬菌体抗体库中筛选出表达抗gp96蛋白Fab抗体的阳性克隆,酶切及连接反应构建其可溶性表达噬菌粒,转化至大肠杆菌BL21(DE3)pLysS中,IPTG诱导特异性抗体的高效表达,并用SDS-PAGE鉴定抗体表达情况、ELISA鉴定其抗原结合活性及特异性；所得抗体经纯化后作为偶联配体,吸附纯化膀胱癌及其癌旁组织中的gp96—肽复合物；通过酸洗脱法得到gp96所结合的多肽片段,经基质辅助激光解析电离飞行时间质谱测定其分子量及氨基酸序列；应用生物信息学技术分析各多肽片段的生物学特性。
结果
1通过对人天然Fab段噬菌体抗体库的四轮淘选,特异性抗gp96蛋白Fab噬菌体抗体得到了富集；
2构建的抗gp96可溶性Fab抗体表达载体,在IPTG的诱导下得到了抗体的高效表达；进一步应用亲和层析技术得到了纯化的抗gp96可溶性Fab抗体；
3利用基因工程抗体技术结合免疫亲和层析技术,可以从少量膀胱组织中纯化出实验用量的gp96—肽复合物,每克组织可获得约20μg-50μ.g的gp96—肽复合物；
4在膀胱癌及其癌旁组织来源的gp96结合的多肽中,14条多肽的氨基酸序列被鉴定,其中8条来源于膀胱癌,6条来源于癌旁组织,分子量在997.5281Da-2211.33Da之间：5条多肽具有明确的蛋白来源,5条多肽经鉴定具有抗原性。
结论
1利用基因工程抗体技术结合免疫亲和层析技术,可成功的从有限的组织中分离纯化出实验用量的gp96—肽复合物；
2gp96结合肽库中的肽为一些小分子肽片段,长短不一,部分蛋白来源明确,部分多肽具有抗原性,具有潜在的临床应用价值。
Objective It has been known heat shock protein gp96derived from cancer cells or tissues can elicit cancer-specific immunity. Recent studies have indicated that gp96molecules, as a chaperon, participate in the presentation of the associated peptides to T cells through histocompatibility complex class I-restricted antigen presentation pathway. On the basis of these features, gp96can be used for cancer immunotherapy. Though the traditional preparation method of gp96had been developed, it had many limitations and shortage including a limited amount of sample material and the complicated purification procedures. The construction of a new rapid and high effective preparation method is necessary. Further Researches had confirmed that the antigenicity derived from not gp96but gp96associated peptides. The whole peptide pool associated with gp96is the molecular basis of the vaccine preparation and the induction of specific immune reaction. So, to further identify and analyze the gp96-associated peptide pool is very necessary for developing effective cancer vaccine and investigating related mechanism of action.
Methods The specific gp-96clones were screened from a'naive'human Fab fragment phage diasplay library against the immobilized gp-96antigens, then the clones were transformed to the BL21(DE3)pLysS to give high-performance soluble expression of Fab antibodies by using IPTG as inducing agent. Soluble Fab antibodies were purified and acted as couple ligand to adsorb gp96peptide complexes from tissue protein suspensions of bladder cancer and paratumor tissue, gp-96associated peptides were eluted and identified by mass spectrometry. Using bioinformatics technology was used to obtain bionomics of polypeptides
Results
1. Specific anti-gp96Fab antibodies were enriched by screening from a human naive Fab fragment phage antibody library.
2. Soluble expressions of specific anti-gp96Fab antibodies were performed.
3. gp-96peptide complexes can be obtained from small amounts of bladder tissue by antibody library technology and immuno affinity chromatography technology. The preparation was identified by Western blot. One gram tissue can obtain20～50μg gp-96peptide complexes.
4.14peptides were identified,8peptides were from bladder cancer tissue, and others were from paracancerous tissue of bladder. The molecular weight range is997.5281Da～2211.33Da. Protein source and antigenicity were identified.
Conclusions
1. gp-96peptide complexes can be obtained from small amounts of bladder tissue by antibody library technology and immunoaffinity chromatography technology.
2. Peptides in gp-96associated peptide pool are some small molecular peptides, their length is different. Protein sources of some peptides are known, some are unknown. Some peptides have antigenicity. Further analysis must be accomplished before the application in peptide vaccine.
方法用固相化的gp96蛋白从人天然噬菌体抗体库中筛选出表达抗gp96蛋白Fab抗体的阳性克隆,酶切及连接反应构建其可溶性表达噬菌粒,转化至大肠杆菌BL21(DE3)pLysS中,IPTG诱导特异性抗体的高效表达,并用SDS-PAGE鉴定抗体表达情况、ELISA鉴定其抗原结合活性及特异性；所得抗体经纯化后作为偶联配体,吸附纯化膀胱癌及其癌旁组织中的gp96—肽复合物；通过酸洗脱法得到gp96所结合的多肽片段,经基质辅助激光解析电离飞行时间质谱测定其分子量及氨基酸序列；应用生物信息学技术分析各多肽片段的生物学特性。
结果
1通过对人天然Fab段噬菌体抗体库的四轮淘选,特异性抗gp96蛋白Fab噬菌体抗体得到了富集；
2构建的抗gp96可溶性Fab抗体表达载体,在IPTG的诱导下得到了抗体的高效表达；进一步应用亲和层析技术得到了纯化的抗gp96可溶性Fab抗体；
3利用基因工程抗体技术结合免疫亲和层析技术,可以从少量膀胱组织中纯化出实验用量的gp96—肽复合物,每克组织可获得约20μg-50μ.g的gp96—肽复合物；
4在膀胱癌及其癌旁组织来源的gp96结合的多肽中,14条多肽的氨基酸序列被鉴定,其中8条来源于膀胱癌,6条来源于癌旁组织,分子量在997.5281Da-2211.33Da之间：5条多肽具有明确的蛋白来源,5条多肽经鉴定具有抗原性。
结论
1利用基因工程抗体技术结合免疫亲和层析技术,可成功的从有限的组织中分离纯化出实验用量的gp96—肽复合物；
2gp96结合肽库中的肽为一些小分子肽片段,长短不一,部分蛋白来源明确,部分多肽具有抗原性,具有潜在的临床应用价值。
Objective It has been known heat shock protein gp96derived from cancer cells or tissues can elicit cancer-specific immunity. Recent studies have indicated that gp96molecules, as a chaperon, participate in the presentation of the associated peptides to T cells through histocompatibility complex class I-restricted antigen presentation pathway. On the basis of these features, gp96can be used for cancer immunotherapy. Though the traditional preparation method of gp96had been developed, it had many limitations and shortage including a limited amount of sample material and the complicated purification procedures. The construction of a new rapid and high effective preparation method is necessary. Further Researches had confirmed that the antigenicity derived from not gp96but gp96associated peptides. The whole peptide pool associated with gp96is the molecular basis of the vaccine preparation and the induction of specific immune reaction. So, to further identify and analyze the gp96-associated peptide pool is very necessary for developing effective cancer vaccine and investigating related mechanism of action.
Methods The specific gp-96clones were screened from a'naive'human Fab fragment phage diasplay library against the immobilized gp-96antigens, then the clones were transformed to the BL21(DE3)pLysS to give high-performance soluble expression of Fab antibodies by using IPTG as inducing agent. Soluble Fab antibodies were purified and acted as couple ligand to adsorb gp96peptide complexes from tissue protein suspensions of bladder cancer and paratumor tissue, gp-96associated peptides were eluted and identified by mass spectrometry. Using bioinformatics technology was used to obtain bionomics of polypeptides
Results
1. Specific anti-gp96Fab antibodies were enriched by screening from a human naive Fab fragment phage antibody library.
2. Soluble expressions of specific anti-gp96Fab antibodies were performed.
3. gp-96peptide complexes can be obtained from small amounts of bladder tissue by antibody library technology and immuno affinity chromatography technology. The preparation was identified by Western blot. One gram tissue can obtain20～50μg gp-96peptide complexes.
4.14peptides were identified,8peptides were from bladder cancer tissue, and others were from paracancerous tissue of bladder. The molecular weight range is997.5281Da～2211.33Da. Protein source and antigenicity were identified.
Conclusions
1. gp-96peptide complexes can be obtained from small amounts of bladder tissue by antibody library technology and immunoaffinity chromatography technology.
2. Peptides in gp-96associated peptide pool are some small molecular peptides, their length is different. Protein sources of some peptides are known, some are unknown. Some peptides have antigenicity. Further analysis must be accomplished before the application in peptide vaccine.
引文
1. Berwin B, Rosser MF, Brinker KG, et al. Transfer of GRP94 (Gp96)-associated peptides onto endosomal MHC class I molecules [J]. Traffic,2002,3(5):358-366.
2. Bausinger H, Lipsker D, Hanau D. Heat shock proteins as activators of the innate immune system [J]. Trends Immunol,2002,23(7):342-343.
3. Basu S, Binder RJ, Suto R, et al. Necrotic but not apoptotic cell death release heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway [J]. Int Immunol,2000,12(11):1539-1546.
4. Robert J, Menoret A, Cohen N. Cell surface expression of the endoplasmic reticularheat shock protein gp96 is phylogenetically conserved [J]. J Immunol, 1999,163(8):4133-4139.
5. Caudill MM, Li Z. HSPPC-96:a personalised cancer vaccine [J]. Exp Opin Biol Ther,2001,1(3):539-548.
6. Chandawarkar RY, Wagh MS, Srivastava PK.The dual nature of specific immunological activity of tumor-derived gp96 preparations [J]. J Exp Med,1999, 189(9):1437-1442.
7. Amato RJ, Savary C, Tomasovic S, et al. Active specific immunotherapy in patients with renal cell carcinoma using autologous tumor derived heat shock protein peptide complex 96 vaccine [J]. Cell Stress Chaperones,2000,5(4):373-397.
8. Aalamian M, Fuchs E, Gupta R, et al. Autologous renal cell cancer vaccines using heat shock protein-peptide complexes [J]. Urol Oncol.2006,24(5):425-433.
9. Srivastava PK. Therapeutic cancer vaccines [J].Curr. Opin. Immunol,2006,18(2): 201-205.
10. Gordon NF, Clark BL. The challenges of bringing autologous HSP-based vaccines to commercial reality [J]. Methods,2004,32(1):63-69.
11. BrissetTE R, Prendergast JK, Goldstein NI. Identification of cancer targets and therapeutics using phage display [J]. Curr. Opin. Drug Discov. Devel.2006,9(3): 363-369.
12. Winter G, Griffiths AD, Hawkins RE, et al. Making antibodies by phage display technology [J]. Annu Rev Immunol,1994,12:433-455.
13.张春莉,王妍.抗体库技术.微生物学免疫学进展[J].2001,29(4)：86-89.
14. Willats WG. Phage display:practicalities and prospects [J]. Plant Mol Biol,2002, 50(6):837-854.
15. Kretzschmar T, von Ruden T. Antibody discovery:phage display [J].Curr Opin Biotechnol,2002,13(6):598-602.
16. Hoogenboom HR. Overview of antibody phage-display technology and its applications [J]. Methods Mol Biol,2002,178:1-37.
17.马小兵,畅继武,王海涛等.人天然Fab段噬菌体抗体库的构建[J].山东医药,2005,45(35)：12-14.
18.张爱华,余模松.噬菌体抗体库技术.国际生物制品学杂志[J].2006,29(1)：13-16.
19. Kramer K, Fiedler M, Skerra A, et al. A generic strategy for subcloning antibody variable regions from the scFv phage display vector pCANTAB 5 E into pASK85 permits the economical production of F(ab) fragments and leads to improved recombinant immunoglobulin stability [J]. Biosens Bioelectron,2002,17(4):305-313.
20. Chanock RM, Crowe JE Jr, Murphy BR, et al. Human monoclonal antibody Fab fragments cloned from combinatorial libraries:potential usefulness in prevention and/or treatment of major human viral diseases [J]. Infect Agents Dis,1993,2(3): 118-131.
21. Barbas CF 3rd, Kang AS, Lerner RA, et al.Assembly of combinatorial antibody libraries on phage surfaces:the gene Ⅲ site [J]. Proc Natl Acad Sci U S A,1991, 88(18):7978-7982.
22.戴和平,高宏,赵新颜.噬菌体展示技术的原理和方法[J].水生生物学报,2002,26(4)：400-409.
23.李承新,刘玉峰,王刚等.基因工程技术制备的人源性抗Mr43角蛋白抗体Fab片段的纯化与活性鉴定[J].第四军医大学学报,2001,22(13)：1157-1160.
24. Srivastava PK. Purification of heat shock protein-peptide complexes for use in vaccination against cancers and intracellular pathogens [J]. Methods,1997,12(2): 165-171.
25. Arnold-Schild D, Kleist C, Welschof M, et al. One-step single-chain Fv recombinant antibody-based purification of gp96 for vaccine development [J]. Cancer Res,2000,60(15):4175-4178.
26. Janetzki S, Palla D, Rosenhauer V, et al. Immunization of cancer patient with autolgous cancer-derived heat shock protein gp96 preparations:A pilot study [J]. Int J Cancer,2000,88(2):232-238.
27. Menoret A, Chandawarkar R. Heat-shock protein-based anticancer immunotherapy:an idea whose time has come [J]. Semin Oncol,1998,25(6):654-660.
28. Sastry S, Linderoth N. Molecular mechanisms of peptide loading by the tumor rejection antigen/heat shock chaperone gp96(GRP94) [J]. J Biol Chem,1999,274 (17):12023-12035.
29. Csermely P, Schnaider T, Soti C, et al. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review [M]. Pharmacol Ther,1998,79:129-168
30. Meng SD, Song J, Rao ZH, et al. Three-step purification of gp96 from human liver tumor tissues suitable for isolation of gp96-bound peptides[J]. J Immunol Methods,2002,264(1-2):29-35.
31. Srivasava PK, Deleo AB, Old LJ. Tumor rejection antigens of chemically induced sarcomas of inbred mice [J]. Proc Natl Acad Sci USA,1986,83(10):3407-3411.
32. Srivastava PK. Peptide-binding heat shock proteins in the endoplasmic reticulum: role in immune response to cancer and in antigen presentation [J]. Adv Cancer Res,1993,62:153-177.
33. Ishii T, Udono H,Yamano T, et al. Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock protein hsp70, hsp90, and gp96 [J]. J Immunol,1999,162(3):1303-1309.
34. Sponaas AM, uegel UZ, Weber S, et al. Immunization with gp96 from Listeria monocytogenes-Infected Mice is due to N-Formylated Listerial peptides [J]. J Immunol,2001,167(11):6480-6486.
35. Liu CL, Nigel Ewing, Melissa DeFilippo. Analytical challenges and strategies for the characterization of gp96-associated peptides [J]. Methods,2004,32(1):32-37.
36. Wang XY, Kaneko Y, Repasky E, et al. Heat shock proteins and cancer immunotherapy [J]. Immunol Invest,2000,29(2):131-137.
37. Heike M, Noll B, Meyer zum Buschenfelde KH. Heat shock protein peptide complexes for use in vaccines [J]. J Leukoc Biol,1996,60(2):153-158.
38. Srivastava PK, Menoret A, Basu S, et al. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world [J]. Immunity,1998, 8(6):657-665.
39. Demine R, Walden P. Testing the role of gp96 as peptide chaperone in antigen processing [J]. J Biol Chem,2005,280(18):17573-17578.
40. Linderoth NA, Simon MN, Hainfeld JF, et al. Binding of antigenic peptide to the endoplasmatic reticulum-resident protein gp96/GRP94 heat shock chaperone occurs in higher order complexes [J]. J Biol Chem,2001,276(14):11049-11054.
41.Kolaskar AS, Tongaonkar PC. A semi-empirical method for prediction of antigenic determinants on protein antigens [J]. FEBS Lett.1990,276(1-2):172-174.
42. Blachere NE, Li Z, Chandawarkar RY, et al. Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity [J]. J Exp Med,1997,186(8):1315-1322.
43. Srivastava P. Interaction of heat shock proteins with peptides and antigen presenting cells:chaperoning of the innate and adaptive immune responses [J]. Annu Rev Immunol,2002,20:395-425.
44. Binder RJ, Srivastava PK. CD91:a receptor for heat shock protein gp96 [J]. Nat Immunol,2000,1(2):151-155.
1. Srivastava PK. Therapeutic cancer vaccines [J]. Curr Opin Immunol.2006,18(2): 201-205.
2. Srivastava PK. Immunotherapy for human cancer using heat shock protein--peptide complexes [J]. Curr Oncol Rep.2005,7(2):104-108.
3. Srivastava PK. Heat shock protein-based novel immunotherapies [J]. Drug News Perspect,2000,13 (9):517-522.
4. Berwin B, Rosser MF, Brinker KG, et al. Transfer of GRP94 (Gp96)-associated peptides onto endosomal MHC class I molecules [J]. Traffic,2002,3(5):358-366.
5. Parmiani G, Testori A, Maio M, et al. Heat shock proteins and their use as anticancer vaccines [J]. Clin Cancer Res.2004,10(24):8142-8146.
6. Castelli C, Rivoltini L, Rini F, et al.Heat shock proteins:biological functions and clinical application as personalized vaccines for human cancer [J].Cancer Immunol Immunother.2004,53(3):227-233.
7. Tamura Y, Peng P, Liu K,et al. Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations [J]. Science.1997,278 (5335): 117-120.
8. Linderoth NA, Popowicz A, Sastry S. Identification of the peptide binding site in the heat shock protein chaperone/tumor rejection antigen gp96(grp94)[J].J Biol Chem,2000,275(8):5472-5477.
9. Demine R, Walden P. Testing the role of gp96 as peptide chaperone in antigen processing [J]. J Biol Chem,2005,280(18):17573-17578.
10. Binder RJ, Ha n D K, Srivastava PK. CD91:a receptor f or heat shock protein gp96 [J]. Nat Immunol,2000,1 (2):151-155.
11. Binder RJ, Srivastava PK. Peptides chaperoned by heat-shock proteins are a necessary and sufficient source of antigen in the cross-priming of CD8+T cells [J]. Nat Immunol.2005,6(6):593-599.
12. Clayton A, Tur kes A, Navabi H, et al. Induction of heat shock proteins in B-cell exosomes [J]. J Cell Sci,2005,118(16):3631-3638.
13. SenGupta D, Norris PJ, Suscovich TJ,et al. Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II [J]. 2004,173(3):1987-1993.
14. Vabulus RM, Braedel S, Hilf N, et al. The endoplamic reticulum-resident heat shock protein gp96 activiate dendritic cells via the Toll-like receptor 2/4 pathway [J]. J Biol Chem,2002,277 (23):20847-20853.
15. Caba nes D, Sousa S, Cebria A, et al. Gp96 is a receptor for a novel Listeria monocytogenes virulence factor, Vip, a surface protein [J]. EMBO Journal,2005, 24(15):2827-2838.
16. Reed RC, Berwin B, Ba ker J P, et al. GRP94/gp96 elicits ERK activation in murine macrop hage:a role for endotoxin contamination in NF2κB activation and nitricoxide production [J]. J Biol Chem,2003,278(34):31853-31860.
17. Panjwani NN, Popova L, Srivastava PK. Heat shock protein gp96 and hsp70 activate the release of nitricoxide by APCs [J]. J Immunol,2002,168 (6):2997-3003.
18. Srivastava PK, Amato RJ. Heat shock proteins:the 'Swiss Army Knife' vaccines against cancers and infectious agents. Vaccine [J].2001,19 (17-19):2590-2597.
19. Robert J, Menoret A, Srivastava PK, et al. Immunological properties of heat shock proteins are phylogenetically conserved [J]. Adv Exp Med Biol.2001,484: 237-249.
20. Heike M, Frenzel C. Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer [J]. Int J Cancer.2000,86(4):489-493.
21. Cai JW, Henderson BW, Shen JW, et al. Induction of glucose regulated proteins during growth of a murine tumor. [J]. J Cell Physiol.1993,154 (2):229-237.
22. Dai J, Liu B, Caudill MM, Zheng H, et al. Cell surface expression of heat shock protein gp96 enhances cross-presentation of cellular antigens and the generation of tumor-specific T cell memory [J]. Cancer Immun.2003,28(3):1-8.
23. Liu B, Dai J, Zheng H, et al. Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases [J]. Proc Natl Acad Sci USA,2003,100(26):15824-15829.
24. Wallin RP, Lundgvist A, More SH,et al. Heat-shock proteins as activators of the innate immune system [J]. Trends Immunol,2002,23 (3):130-135.
25. Binder RJ, Srivastava PK.Essential role of CD91 in re-presentation of gp96-chaperoned peptides [J]. Proc Natl Acad Sci U S A.2004,101 (16):6128-6133.
26. Binder RJ, Kumar SK, Srivastava PK. Naturally formed or artificially reconstituted non-covalent alpha2-macroglobulin-peptide complexes elicit CD91-dependent cellular immunity [J]. Cancer Immun.2002,2:16.
27. Binder RJ, Han DK, Srivastava PK. CD91:a receptor for heat shockprotein gp96 [J]. Nat Immunol,2000,1(2):151-155.
28. Binder RJ, Karimeddini D, Srivastava PK. J Immunol. Adjuvanticity of alpha 2-macroglobulin, an independent ligand for the heat shock protein receptor CD91 [J].2001,166(8):4968-4972.
29. Kol A, Lichtman AH, Finberg RW,et al. Cutting edge:heat shock protein (HSP)60 activates the innate immune response:CD14 is an essential receptor for HSP60 activation of mononu-clear cells [J]. J Immunol,2000,164(1):13-17.
30. Beg AA. Endogenous ligands of Toll-like receptors:implications for regulating inflam-matory and immune responses [J]. Trends Immunol,2002,23(11):509-512.
31. Yang Y, Liu B, Dai J, et al. Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages [J]. Immunity.2007,26(2):215-226.
32. Takeda K, Kaisho T, Akira S. Toll-like receptors [J]. Annu Rev Immunol,2003, 21:335-376.
33. Barton GM, Medzhitov R. Toll-like receptor signaling pathways [J]. Science, 2003,300(5625):1524-1525.
34. Binder RJ, Vatner R, Srivastava P. The heat-shock protein receptors:some answers and more questions [J].Tissue Antigens.2004,64(4):442-451.
35. Robert J, Menoret A, Basu S, et al. Phylogenetic conservation of the molecular and immunological properties of the chaperones gp96 and hsp70 [J]. Eur J Immunol.2001,31(1):186-95.
36. Ishii T, Udono H, Yamano T, et al. Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96 [J].J Immunol.1999,162(3):1303-1309.
37. Chaput N, Taieb J, Schartz NE, et al. Exosome-based immunotherapy [J]. Cancer Immunol Immunother.2004,53(3):234-239.
38. Somersan S, Larsson M, Fonteneau JF,et al. Primary tumor tissue lysates are enriched in heat shock proteins and induce the maturation of human dendritic cells [J].J Immunol.2001,167(9):4844-4852.
39. Berwin B, Hart JP, Rice S et al. Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells [J]. EMBO J.2003,22 (22):6127-6136.
40. Tsan MF, Gao B. Cytokine function of heat shock proteins [J]. Am J Physiol Cell Physiol,2004,286(4):C 739-744.
41. Li Z, Menoret A, Srivastava PCurr Opin Immunol. Roles of heat-shock proteins in antigen presentation and cross-presentation [J].2002,14(1):45-51.
42. Janetzki S, Blachere NE, Srivastava PKGeneration of tumor-specific cytotoxic T lymphocytes and memory T cells by immunization with tumor-derived heat shock protein gp96 [J].J Immunother (1997).1998,21(4):269-76.
43. Goyos A, Cohen N, Gantress J, et al. Anti-tumor MHC class la-unrestricted CD8 T cell cytotoxicity elicited by the heat shock protein gp96 [J]. Eur J Immunol,2004,34 (9):2449-2458.
44. Levey DL, Udono H, Heike M,et al. Identification of a tumor-associated contact-dependent activity which reversibly downregulates cytolytic function of CD8+T cells [J]. Cancer Immun.2001,1:5.
45. Blachere NE, Li Z, Chandawarkar RY, et alHeat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity [J]. J Exp Med.1997,186(8):1315-22.
46. Linderoth NA, Simon MN, Rodionova NA,et al. Biophysical analysis of the endoplasmic reticulum-resident chaperone/heat shock protein gp96/GRP94 and its complex with peptide antigen [J]. Biochem,2001,40 (5):1483-1495.
47. Adams EJ, Chien YH, Garcia KC. Structure of a gammadelta T cell receptor in complex with the nonclassical MHC [J]. Science,2005,308 (5719):227-231.
48. Srivastava P. Interaction of heat shock proteins with peptides and antigen presenting cells:chaperoning of the innate and adaptive immune responses [J]. Annu Rev Immunol.2002,20:395-425.
49. Anderson KM, Srivastava PK. Heat, heat shock, heat shock proteins and death:a central link in innate and adaptive immune responses [J]. Immunol Lett.2000, 74(1):35-39.
50. Baker-LePain JC, Reed RC, Nicchitta CV. ISO:a critical evaluation of the role of peptides in heat shock/chaperone protein-mediated tumor rejection [J]. Curr Opin Immunol.2003,15(1):89-94.
51. Srivastava PK. Hypothesis:controlled necrosis as a tool for immunotherapy of human cancer [J]. Cancer Immun.2003,3:4.
52. Strbo N, Oizumi S, Sotosek-Tokmadzic V, et al. Perforin is required for innate and adaptive immunity induced by heat shock protein gp96 [J]. Immunity.2003, 18(3):381-390.
53. Binder RJ, Blachere NE, Srivastava PK Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules [J]. J Biol Chem.2001,276(20): 17163-17171.
54. Menoret A, Peng P, Srivastava PK. Association of peptides with heat shock protein gp96 occurs in vivo and not after cell lysis [J]. Biochem Biophys Res Commun.1999,262(3):813-818.
55. Srivastava PK Immunotherapy of human cancer:lessons from mice.Nat Immunol. 2000, 1(5):363-366.
56. Reed RC, Zheng T, Nicchitta CV. GRP94-associated enzymatic activities. Resolution by chromatographic fractionation [J]. J Biol Chem.2002,277(28): 25082-25089.
57. Binder RJ, Anderson KM, Basu S, Cutting edge:heat shock protein gp96 induces maturation and migration of CD11c+ cells in vivo [J]. J Immunol.2000,165(11): 6029-6035.
58. Feldweg AM, Srivastava PK Molecular heterogeneity of tumor rejection antigen /heat shock protein GP96 [J]. Int J Cancer.1995,63(2):310-314.
59. Basu S, Binder RJ, Ramalingam T,et al. CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin [J]. Immunity,2001,14 (3): 303-313.
60. Related Articles, Banerjee PP, Vinay DS, et al. Evidence that glycoprotein 96 (B2), a stress protein, functions as a Th2-specific costimulatory molecule [J].J Immunol.2002,169(7):3507-3518.
61. Radsak MP, Hilf N, Singh-Jasuja H,et al. The heat shock protein Gp96 binds to human neutrophils and monocytes and stimulates effector functions [J]. Blood. 2003,101(7):2810-2815.
62. Baker-LePain JC, Sarzotti M, Fields TA, et al. GRP94 (gp96) and GRP94 N-terminal geldanamycin binding domain elicit tissue nonrestricted tumor suppression [J]. J Exp Med.2002,196(11):1447-1459.
63. Related Articles, Reits E, Griekspoor A, et al. Peptide diffusion, protection, and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class Ⅰ [J]. Immunity.2003,18(1):97-108.
64. Zheng H, Dai J, Stoilova D, et al. Cell surface targeting of heat shock protein gp96 activates dendritic cells via the toll-like receptor 2/4 pathway [J].2001,67 (10):6731-6735.
65. Gao B, Tsan MF. Endotoxin contamination in recombinant human heat shock protein 70 (Hsp70) preparation is responsible for the induction of tumor necrosis factor alpha release by murine macrophages [J]. J Biol Chem,2003,278(1): 174-179.
66. Binder RJ, Kelly JB 3rd, Vatner RE, et al. Specific immunogenicity of heat shock protein gp96 derives from chaperoned antigenic peptides and not from contaminating proteins [J]. J Immunol.2007,179(11):7254-7261.
67. Baker-LePain JC, Sarzotti M, Nicchitta CV. Glucose-regulated protein 94/glycoprotein 96 elicits bystander activation of CD4+ T cell Thl cytokine production in vivo [J]. J Immunol.2004,172 (7):4195-4203.
68. Blachere NE, Li Z, Chandawarkar RY, et al. Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity [J]. J Exp Med,1997,20,186(8):1315-1322.
69. Srivastava P. Interaction of heat shock proteins with peptides and antigen presenting cells:chaperoning of the innate and adaptive immune responses [J]. Annu Rev Immunol,2002,20:395-425.
70. Wang XY, Kaneko Y, Repasky E, et al. Heat shock proteins and cancer immunotherapy [J]. Immunol Invest,2000,29(2):131-137.
71. Heike M, Noll B, Meyer zum Buschenfelde KH. Heat shock protein peptide complexes for use in vaccines [J]. J Leukoc Biol,1996,60(2):153-158.
72. Srivastava PK, Menoret A, Basu S, et al. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world [J]. Immunity,1998, 8(6):657-665.
73. Liu CL, Nigel Ewing, Melissa DeFilippo. Analytical challenges and strategies for the characterization of gp96-associated peptides [J]. Methods,2004,32:32-37.
74. Linderoth NA, Simon MN, Hainfeld JF, et al. Binding of antigenic peptide to the endoplasmatic reticulum-resident protein gp96/GRP94 heat shock chaperone occurs in higher order complexes [J]. J Biol Chem,2001,276:11049-11054.
75. Srivastava PK. Purification of immunogenic heat shock protein 70-peptide complexes by ADP-affinity chromatography [J]. J Immunol Methods.1997, 204(1):13-21.
76. Srivastava PK, Jaikaria NS. Methods of purification of heat shock protein-peptide complexes for use as vaccines against cancers and infectious diseases [J]. Methods Mol Biol.2001,156:175-86.
77. Peng P, Menoret A, Robert J, Menoret A, Cohen N. Cell surface expression of the endoplasmic reticularheat shock protein gp96 is phylogenetically conserved[J]. J Immunol,1999,163:4133-4139.
78.周先碗,胡晓倩.生物化学仪器分析与实验技术[M].北京：化学工业出版社,2002：90-92.
79. Srivastava PK. Purification of heat shock protein-peptide complexes for use in vaccination against cancers and intracellular pathogens [J]. Methods,1997,12: 165-171.
80. Arnold D, Faath S, Rammensee H, et al. Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96 [J]. J Exp Med,1995,82:885-889.
81. Bethke K, Staib F, Distler M, et al. Different efficiency of heat shock proteins (HSP) to activate human monocytes and dendritic cells:superiority of HSP60 [J]. J Immunol,2002,169:6141-6148.
82. Menoret A, Chandawarkar R. Heat-shock protein-based anticancer immunotherapy:an idea whose time has come [J]. Semin Oncol,1998,25:654-660.
83. Sastry S, Linderoth N. Molecular mechanisms of peptide loading by the tumor rejection antigen/heat shock chaperone gp96(GRP94) [J]. J Biol Chem,1999, 274:12023-12035.
84. Csermely P, Schnaider T, Soti C, et al. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review [J]. Pharmacol Ther,1998,79:129-168.
85. Asea A, Rehli M, Kabingu E, et al. Novel signal transduction pathway utilized by extracellular HSP70:role of toll-like receptor(TLR) 2 and TLR4 [J]. J Biol Chem,2002,277(17):15028-15034.
86. Janetzki S, Palla D, Rosenhauer V, et al.Immunization of cancer patients with autologous cancer-derived heat shock protein gp96 preparations:a pilot study [J]. Int J Cancer.2000,88(2):232-238.
87. Mazzaferro V, Coppa J, Carrabba MG, et al. Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer [J]. Clin Cancer Res.2003,9(9):3235-3245.
88. Rivoltini L, Castelli C, Carrabba M, et al. Human tumor-derived heat shock protein 96 mediates in vitro activation and in vivo expansion of melanoma-and colon carcinoma-specific T cells [J]., J Immunol.2003,171(7):3467-3474.
89. Fleischer K, Schmidt B, Kastenmtiller W, et al. Melanoma-reactive class I-restricted cytotoxic T cell clones are stimulated by dendritic cells loaded with synthetic peptides, but fail to respond to dendritic cells pulsed with melanoma-derived heat shock proteins in vitro [J]. J Immunol.2004,172(1): 162-169.
90. Menoret A, Chandawarkar RY, Srivastava PK. Natural autoantibodies against heat-shock proteins hsp70 and gp96:implications for immunotherapy using heat-shock proteins [J]. Immunology,2000,101(3):364-370.
91. Arnold-Schild D, Kleist C, Welschof M, et al. One-step single-chain Fv recombinant antibody-based purification of gp96 for vaccine development [J]. Cancer Res,2000,60(15):4175-4178.
92. Berwin B, Reed RC, Nicchitta CV. Virally induced lytic cell death elicits the release of immunogenic GRP94/gp96 [J].J Biol Chem,2001,276(24):21083-21088.
93. Belli F, Testori A, Rivoltini L, et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings [J]. J Clin Oncol.2002,20(20):4169-4180.
94. Makki A, Weidt G, Blachere NE, et al. Immunization against a dominant tumor antigen abrogates immunogenicity of the tumor [J].Cancer Immun.2002,16,2-4.
95. Stebbing J, Bower M, Srivastava P. Kaposi's sarcoma as a model for cancer immunotherapy [J]. Trends Mol Med.2004,10(4):187-193.
96. Srivastava P. Heat shock proteins and immune response:methods to madness [J]. Methods.2004,32(1):1-2.
97. Maki RG, Livingston PO, Lewis JJ, et al. A phase I pilot study of autologous heat shock protein vaccine HSPPC-96 in patients with resected pancreatic adenocarcinoma [J]. Dig Dis Sci.2007,52(8):1964-1972.
98. Oki Y, McLaughlin P, Fayad LE, et al. Experience with heat shock protein-peptide complex 96 vaccine therapy in patients with indolent non-Hodgkin lymphoma [J]. Cancer.2007,109(1):77-83.
99. Yedavelli SP, Guo L, Daou ME, et al. Preventive and therapeutic effect of tumor derived heat shock protein, gp96, in an experimental prostate cancer model [J]. Int J Mol Med.1999,4(3):243-248.
100. Przepiorka D, Srivastava PKHeat shock protein--peptide complexes as immunotherapy for human cancer [J]. Mol Med Today.1998,4(11):478-484.
101. Srivastava PK, Menoret A, Basu S, et al. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world [J]. Immunity.1998, 8(6):657-665.
102. Chandawarkar RY, Wagh MS, Srivastava PK. The dual nature of specific immunological activity of tumor-derived gp96 preparations [J]. J Exp Med.1999, 189(9):1437-1442.
103.Srivastava PK, Kozak CA, Old LJ. Chromosomal assignment of the gene encoding the mouse tumor rejection antigen gp96 [J]. Immunogenetics.1988, 28(3):205-207.
2. Bausinger H, Lipsker D, Hanau D. Heat shock proteins as activators of the innate immune system [J]. Trends Immunol,2002,23(7):342-343.
3. Basu S, Binder RJ, Suto R, et al. Necrotic but not apoptotic cell death release heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway [J]. Int Immunol,2000,12(11):1539-1546.
4. Robert J, Menoret A, Cohen N. Cell surface expression of the endoplasmic reticularheat shock protein gp96 is phylogenetically conserved [J]. J Immunol, 1999,163(8):4133-4139.
5. Caudill MM, Li Z. HSPPC-96:a personalised cancer vaccine [J]. Exp Opin Biol Ther,2001,1(3):539-548.
6. Chandawarkar RY, Wagh MS, Srivastava PK.The dual nature of specific immunological activity of tumor-derived gp96 preparations [J]. J Exp Med,1999, 189(9):1437-1442.
7. Amato RJ, Savary C, Tomasovic S, et al. Active specific immunotherapy in patients with renal cell carcinoma using autologous tumor derived heat shock protein peptide complex 96 vaccine [J]. Cell Stress Chaperones,2000,5(4):373-397.
8. Aalamian M, Fuchs E, Gupta R, et al. Autologous renal cell cancer vaccines using heat shock protein-peptide complexes [J]. Urol Oncol.2006,24(5):425-433.
9. Srivastava PK. Therapeutic cancer vaccines [J].Curr. Opin. Immunol,2006,18(2): 201-205.
10. Gordon NF, Clark BL. The challenges of bringing autologous HSP-based vaccines to commercial reality [J]. Methods,2004,32(1):63-69.
11. BrissetTE R, Prendergast JK, Goldstein NI. Identification of cancer targets and therapeutics using phage display [J]. Curr. Opin. Drug Discov. Devel.2006,9(3): 363-369.
12. Winter G, Griffiths AD, Hawkins RE, et al. Making antibodies by phage display technology [J]. Annu Rev Immunol,1994,12:433-455.
13.张春莉,王妍.抗体库技术.微生物学免疫学进展[J].2001,29(4)：86-89.
14. Willats WG. Phage display:practicalities and prospects [J]. Plant Mol Biol,2002, 50(6):837-854.
15. Kretzschmar T, von Ruden T. Antibody discovery:phage display [J].Curr Opin Biotechnol,2002,13(6):598-602.
16. Hoogenboom HR. Overview of antibody phage-display technology and its applications [J]. Methods Mol Biol,2002,178:1-37.
17.马小兵,畅继武,王海涛等.人天然Fab段噬菌体抗体库的构建[J].山东医药,2005,45(35)：12-14.
18.张爱华,余模松.噬菌体抗体库技术.国际生物制品学杂志[J].2006,29(1)：13-16.
19. Kramer K, Fiedler M, Skerra A, et al. A generic strategy for subcloning antibody variable regions from the scFv phage display vector pCANTAB 5 E into pASK85 permits the economical production of F(ab) fragments and leads to improved recombinant immunoglobulin stability [J]. Biosens Bioelectron,2002,17(4):305-313.
20. Chanock RM, Crowe JE Jr, Murphy BR, et al. Human monoclonal antibody Fab fragments cloned from combinatorial libraries:potential usefulness in prevention and/or treatment of major human viral diseases [J]. Infect Agents Dis,1993,2(3): 118-131.
21. Barbas CF 3rd, Kang AS, Lerner RA, et al.Assembly of combinatorial antibody libraries on phage surfaces:the gene Ⅲ site [J]. Proc Natl Acad Sci U S A,1991, 88(18):7978-7982.
22.戴和平,高宏,赵新颜.噬菌体展示技术的原理和方法[J].水生生物学报,2002,26(4)：400-409.
23.李承新,刘玉峰,王刚等.基因工程技术制备的人源性抗Mr43角蛋白抗体Fab片段的纯化与活性鉴定[J].第四军医大学学报,2001,22(13)：1157-1160.
24. Srivastava PK. Purification of heat shock protein-peptide complexes for use in vaccination against cancers and intracellular pathogens [J]. Methods,1997,12(2): 165-171.
25. Arnold-Schild D, Kleist C, Welschof M, et al. One-step single-chain Fv recombinant antibody-based purification of gp96 for vaccine development [J]. Cancer Res,2000,60(15):4175-4178.
26. Janetzki S, Palla D, Rosenhauer V, et al. Immunization of cancer patient with autolgous cancer-derived heat shock protein gp96 preparations:A pilot study [J]. Int J Cancer,2000,88(2):232-238.
27. Menoret A, Chandawarkar R. Heat-shock protein-based anticancer immunotherapy:an idea whose time has come [J]. Semin Oncol,1998,25(6):654-660.
28. Sastry S, Linderoth N. Molecular mechanisms of peptide loading by the tumor rejection antigen/heat shock chaperone gp96(GRP94) [J]. J Biol Chem,1999,274 (17):12023-12035.
29. Csermely P, Schnaider T, Soti C, et al. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review [M]. Pharmacol Ther,1998,79:129-168
30. Meng SD, Song J, Rao ZH, et al. Three-step purification of gp96 from human liver tumor tissues suitable for isolation of gp96-bound peptides[J]. J Immunol Methods,2002,264(1-2):29-35.
31. Srivasava PK, Deleo AB, Old LJ. Tumor rejection antigens of chemically induced sarcomas of inbred mice [J]. Proc Natl Acad Sci USA,1986,83(10):3407-3411.
32. Srivastava PK. Peptide-binding heat shock proteins in the endoplasmic reticulum: role in immune response to cancer and in antigen presentation [J]. Adv Cancer Res,1993,62:153-177.
33. Ishii T, Udono H,Yamano T, et al. Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock protein hsp70, hsp90, and gp96 [J]. J Immunol,1999,162(3):1303-1309.
34. Sponaas AM, uegel UZ, Weber S, et al. Immunization with gp96 from Listeria monocytogenes-Infected Mice is due to N-Formylated Listerial peptides [J]. J Immunol,2001,167(11):6480-6486.
35. Liu CL, Nigel Ewing, Melissa DeFilippo. Analytical challenges and strategies for the characterization of gp96-associated peptides [J]. Methods,2004,32(1):32-37.
36. Wang XY, Kaneko Y, Repasky E, et al. Heat shock proteins and cancer immunotherapy [J]. Immunol Invest,2000,29(2):131-137.
37. Heike M, Noll B, Meyer zum Buschenfelde KH. Heat shock protein peptide complexes for use in vaccines [J]. J Leukoc Biol,1996,60(2):153-158.
38. Srivastava PK, Menoret A, Basu S, et al. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world [J]. Immunity,1998, 8(6):657-665.
39. Demine R, Walden P. Testing the role of gp96 as peptide chaperone in antigen processing [J]. J Biol Chem,2005,280(18):17573-17578.
40. Linderoth NA, Simon MN, Hainfeld JF, et al. Binding of antigenic peptide to the endoplasmatic reticulum-resident protein gp96/GRP94 heat shock chaperone occurs in higher order complexes [J]. J Biol Chem,2001,276(14):11049-11054.
41.Kolaskar AS, Tongaonkar PC. A semi-empirical method for prediction of antigenic determinants on protein antigens [J]. FEBS Lett.1990,276(1-2):172-174.
42. Blachere NE, Li Z, Chandawarkar RY, et al. Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity [J]. J Exp Med,1997,186(8):1315-1322.
43. Srivastava P. Interaction of heat shock proteins with peptides and antigen presenting cells:chaperoning of the innate and adaptive immune responses [J]. Annu Rev Immunol,2002,20:395-425.
44. Binder RJ, Srivastava PK. CD91:a receptor for heat shock protein gp96 [J]. Nat Immunol,2000,1(2):151-155.
1. Srivastava PK. Therapeutic cancer vaccines [J]. Curr Opin Immunol.2006,18(2): 201-205.
2. Srivastava PK. Immunotherapy for human cancer using heat shock protein--peptide complexes [J]. Curr Oncol Rep.2005,7(2):104-108.
3. Srivastava PK. Heat shock protein-based novel immunotherapies [J]. Drug News Perspect,2000,13 (9):517-522.
4. Berwin B, Rosser MF, Brinker KG, et al. Transfer of GRP94 (Gp96)-associated peptides onto endosomal MHC class I molecules [J]. Traffic,2002,3(5):358-366.
5. Parmiani G, Testori A, Maio M, et al. Heat shock proteins and their use as anticancer vaccines [J]. Clin Cancer Res.2004,10(24):8142-8146.
6. Castelli C, Rivoltini L, Rini F, et al.Heat shock proteins:biological functions and clinical application as personalized vaccines for human cancer [J].Cancer Immunol Immunother.2004,53(3):227-233.
7. Tamura Y, Peng P, Liu K,et al. Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations [J]. Science.1997,278 (5335): 117-120.
8. Linderoth NA, Popowicz A, Sastry S. Identification of the peptide binding site in the heat shock protein chaperone/tumor rejection antigen gp96(grp94)[J].J Biol Chem,2000,275(8):5472-5477.
9. Demine R, Walden P. Testing the role of gp96 as peptide chaperone in antigen processing [J]. J Biol Chem,2005,280(18):17573-17578.
10. Binder RJ, Ha n D K, Srivastava PK. CD91:a receptor f or heat shock protein gp96 [J]. Nat Immunol,2000,1 (2):151-155.
11. Binder RJ, Srivastava PK. Peptides chaperoned by heat-shock proteins are a necessary and sufficient source of antigen in the cross-priming of CD8+T cells [J]. Nat Immunol.2005,6(6):593-599.
12. Clayton A, Tur kes A, Navabi H, et al. Induction of heat shock proteins in B-cell exosomes [J]. J Cell Sci,2005,118(16):3631-3638.
13. SenGupta D, Norris PJ, Suscovich TJ,et al. Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II [J]. 2004,173(3):1987-1993.
14. Vabulus RM, Braedel S, Hilf N, et al. The endoplamic reticulum-resident heat shock protein gp96 activiate dendritic cells via the Toll-like receptor 2/4 pathway [J]. J Biol Chem,2002,277 (23):20847-20853.
15. Caba nes D, Sousa S, Cebria A, et al. Gp96 is a receptor for a novel Listeria monocytogenes virulence factor, Vip, a surface protein [J]. EMBO Journal,2005, 24(15):2827-2838.
16. Reed RC, Berwin B, Ba ker J P, et al. GRP94/gp96 elicits ERK activation in murine macrop hage:a role for endotoxin contamination in NF2κB activation and nitricoxide production [J]. J Biol Chem,2003,278(34):31853-31860.
17. Panjwani NN, Popova L, Srivastava PK. Heat shock protein gp96 and hsp70 activate the release of nitricoxide by APCs [J]. J Immunol,2002,168 (6):2997-3003.
18. Srivastava PK, Amato RJ. Heat shock proteins:the 'Swiss Army Knife' vaccines against cancers and infectious agents. Vaccine [J].2001,19 (17-19):2590-2597.
19. Robert J, Menoret A, Srivastava PK, et al. Immunological properties of heat shock proteins are phylogenetically conserved [J]. Adv Exp Med Biol.2001,484: 237-249.
20. Heike M, Frenzel C. Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer [J]. Int J Cancer.2000,86(4):489-493.
21. Cai JW, Henderson BW, Shen JW, et al. Induction of glucose regulated proteins during growth of a murine tumor. [J]. J Cell Physiol.1993,154 (2):229-237.
22. Dai J, Liu B, Caudill MM, Zheng H, et al. Cell surface expression of heat shock protein gp96 enhances cross-presentation of cellular antigens and the generation of tumor-specific T cell memory [J]. Cancer Immun.2003,28(3):1-8.
23. Liu B, Dai J, Zheng H, et al. Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases [J]. Proc Natl Acad Sci USA,2003,100(26):15824-15829.
24. Wallin RP, Lundgvist A, More SH,et al. Heat-shock proteins as activators of the innate immune system [J]. Trends Immunol,2002,23 (3):130-135.
25. Binder RJ, Srivastava PK.Essential role of CD91 in re-presentation of gp96-chaperoned peptides [J]. Proc Natl Acad Sci U S A.2004,101 (16):6128-6133.
26. Binder RJ, Kumar SK, Srivastava PK. Naturally formed or artificially reconstituted non-covalent alpha2-macroglobulin-peptide complexes elicit CD91-dependent cellular immunity [J]. Cancer Immun.2002,2:16.
27. Binder RJ, Han DK, Srivastava PK. CD91:a receptor for heat shockprotein gp96 [J]. Nat Immunol,2000,1(2):151-155.
28. Binder RJ, Karimeddini D, Srivastava PK. J Immunol. Adjuvanticity of alpha 2-macroglobulin, an independent ligand for the heat shock protein receptor CD91 [J].2001,166(8):4968-4972.
29. Kol A, Lichtman AH, Finberg RW,et al. Cutting edge:heat shock protein (HSP)60 activates the innate immune response:CD14 is an essential receptor for HSP60 activation of mononu-clear cells [J]. J Immunol,2000,164(1):13-17.
30. Beg AA. Endogenous ligands of Toll-like receptors:implications for regulating inflam-matory and immune responses [J]. Trends Immunol,2002,23(11):509-512.
31. Yang Y, Liu B, Dai J, et al. Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages [J]. Immunity.2007,26(2):215-226.
32. Takeda K, Kaisho T, Akira S. Toll-like receptors [J]. Annu Rev Immunol,2003, 21:335-376.
33. Barton GM, Medzhitov R. Toll-like receptor signaling pathways [J]. Science, 2003,300(5625):1524-1525.
34. Binder RJ, Vatner R, Srivastava P. The heat-shock protein receptors:some answers and more questions [J].Tissue Antigens.2004,64(4):442-451.
35. Robert J, Menoret A, Basu S, et al. Phylogenetic conservation of the molecular and immunological properties of the chaperones gp96 and hsp70 [J]. Eur J Immunol.2001,31(1):186-95.
36. Ishii T, Udono H, Yamano T, et al. Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96 [J].J Immunol.1999,162(3):1303-1309.
37. Chaput N, Taieb J, Schartz NE, et al. Exosome-based immunotherapy [J]. Cancer Immunol Immunother.2004,53(3):234-239.
38. Somersan S, Larsson M, Fonteneau JF,et al. Primary tumor tissue lysates are enriched in heat shock proteins and induce the maturation of human dendritic cells [J].J Immunol.2001,167(9):4844-4852.
39. Berwin B, Hart JP, Rice S et al. Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells [J]. EMBO J.2003,22 (22):6127-6136.
40. Tsan MF, Gao B. Cytokine function of heat shock proteins [J]. Am J Physiol Cell Physiol,2004,286(4):C 739-744.
41. Li Z, Menoret A, Srivastava PCurr Opin Immunol. Roles of heat-shock proteins in antigen presentation and cross-presentation [J].2002,14(1):45-51.
42. Janetzki S, Blachere NE, Srivastava PKGeneration of tumor-specific cytotoxic T lymphocytes and memory T cells by immunization with tumor-derived heat shock protein gp96 [J].J Immunother (1997).1998,21(4):269-76.
43. Goyos A, Cohen N, Gantress J, et al. Anti-tumor MHC class la-unrestricted CD8 T cell cytotoxicity elicited by the heat shock protein gp96 [J]. Eur J Immunol,2004,34 (9):2449-2458.
44. Levey DL, Udono H, Heike M,et al. Identification of a tumor-associated contact-dependent activity which reversibly downregulates cytolytic function of CD8+T cells [J]. Cancer Immun.2001,1:5.
45. Blachere NE, Li Z, Chandawarkar RY, et alHeat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity [J]. J Exp Med.1997,186(8):1315-22.
46. Linderoth NA, Simon MN, Rodionova NA,et al. Biophysical analysis of the endoplasmic reticulum-resident chaperone/heat shock protein gp96/GRP94 and its complex with peptide antigen [J]. Biochem,2001,40 (5):1483-1495.
47. Adams EJ, Chien YH, Garcia KC. Structure of a gammadelta T cell receptor in complex with the nonclassical MHC [J]. Science,2005,308 (5719):227-231.
48. Srivastava P. Interaction of heat shock proteins with peptides and antigen presenting cells:chaperoning of the innate and adaptive immune responses [J]. Annu Rev Immunol.2002,20:395-425.
49. Anderson KM, Srivastava PK. Heat, heat shock, heat shock proteins and death:a central link in innate and adaptive immune responses [J]. Immunol Lett.2000, 74(1):35-39.
50. Baker-LePain JC, Reed RC, Nicchitta CV. ISO:a critical evaluation of the role of peptides in heat shock/chaperone protein-mediated tumor rejection [J]. Curr Opin Immunol.2003,15(1):89-94.
51. Srivastava PK. Hypothesis:controlled necrosis as a tool for immunotherapy of human cancer [J]. Cancer Immun.2003,3:4.
52. Strbo N, Oizumi S, Sotosek-Tokmadzic V, et al. Perforin is required for innate and adaptive immunity induced by heat shock protein gp96 [J]. Immunity.2003, 18(3):381-390.
53. Binder RJ, Blachere NE, Srivastava PK Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules [J]. J Biol Chem.2001,276(20): 17163-17171.
54. Menoret A, Peng P, Srivastava PK. Association of peptides with heat shock protein gp96 occurs in vivo and not after cell lysis [J]. Biochem Biophys Res Commun.1999,262(3):813-818.
55. Srivastava PK Immunotherapy of human cancer:lessons from mice.Nat Immunol. 2000, 1(5):363-366.
56. Reed RC, Zheng T, Nicchitta CV. GRP94-associated enzymatic activities. Resolution by chromatographic fractionation [J]. J Biol Chem.2002,277(28): 25082-25089.
57. Binder RJ, Anderson KM, Basu S, Cutting edge:heat shock protein gp96 induces maturation and migration of CD11c+ cells in vivo [J]. J Immunol.2000,165(11): 6029-6035.
58. Feldweg AM, Srivastava PK Molecular heterogeneity of tumor rejection antigen /heat shock protein GP96 [J]. Int J Cancer.1995,63(2):310-314.
59. Basu S, Binder RJ, Ramalingam T,et al. CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin [J]. Immunity,2001,14 (3): 303-313.
60. Related Articles, Banerjee PP, Vinay DS, et al. Evidence that glycoprotein 96 (B2), a stress protein, functions as a Th2-specific costimulatory molecule [J].J Immunol.2002,169(7):3507-3518.
61. Radsak MP, Hilf N, Singh-Jasuja H,et al. The heat shock protein Gp96 binds to human neutrophils and monocytes and stimulates effector functions [J]. Blood. 2003,101(7):2810-2815.
62. Baker-LePain JC, Sarzotti M, Fields TA, et al. GRP94 (gp96) and GRP94 N-terminal geldanamycin binding domain elicit tissue nonrestricted tumor suppression [J]. J Exp Med.2002,196(11):1447-1459.
63. Related Articles, Reits E, Griekspoor A, et al. Peptide diffusion, protection, and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class Ⅰ [J]. Immunity.2003,18(1):97-108.
64. Zheng H, Dai J, Stoilova D, et al. Cell surface targeting of heat shock protein gp96 activates dendritic cells via the toll-like receptor 2/4 pathway [J].2001,67 (10):6731-6735.
65. Gao B, Tsan MF. Endotoxin contamination in recombinant human heat shock protein 70 (Hsp70) preparation is responsible for the induction of tumor necrosis factor alpha release by murine macrophages [J]. J Biol Chem,2003,278(1): 174-179.
66. Binder RJ, Kelly JB 3rd, Vatner RE, et al. Specific immunogenicity of heat shock protein gp96 derives from chaperoned antigenic peptides and not from contaminating proteins [J]. J Immunol.2007,179(11):7254-7261.
67. Baker-LePain JC, Sarzotti M, Nicchitta CV. Glucose-regulated protein 94/glycoprotein 96 elicits bystander activation of CD4+ T cell Thl cytokine production in vivo [J]. J Immunol.2004,172 (7):4195-4203.
68. Blachere NE, Li Z, Chandawarkar RY, et al. Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity [J]. J Exp Med,1997,20,186(8):1315-1322.
69. Srivastava P. Interaction of heat shock proteins with peptides and antigen presenting cells:chaperoning of the innate and adaptive immune responses [J]. Annu Rev Immunol,2002,20:395-425.
70. Wang XY, Kaneko Y, Repasky E, et al. Heat shock proteins and cancer immunotherapy [J]. Immunol Invest,2000,29(2):131-137.
71. Heike M, Noll B, Meyer zum Buschenfelde KH. Heat shock protein peptide complexes for use in vaccines [J]. J Leukoc Biol,1996,60(2):153-158.
72. Srivastava PK, Menoret A, Basu S, et al. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world [J]. Immunity,1998, 8(6):657-665.
73. Liu CL, Nigel Ewing, Melissa DeFilippo. Analytical challenges and strategies for the characterization of gp96-associated peptides [J]. Methods,2004,32:32-37.
74. Linderoth NA, Simon MN, Hainfeld JF, et al. Binding of antigenic peptide to the endoplasmatic reticulum-resident protein gp96/GRP94 heat shock chaperone occurs in higher order complexes [J]. J Biol Chem,2001,276:11049-11054.
75. Srivastava PK. Purification of immunogenic heat shock protein 70-peptide complexes by ADP-affinity chromatography [J]. J Immunol Methods.1997, 204(1):13-21.
76. Srivastava PK, Jaikaria NS. Methods of purification of heat shock protein-peptide complexes for use as vaccines against cancers and infectious diseases [J]. Methods Mol Biol.2001,156:175-86.
77. Peng P, Menoret A, Robert J, Menoret A, Cohen N. Cell surface expression of the endoplasmic reticularheat shock protein gp96 is phylogenetically conserved[J]. J Immunol,1999,163:4133-4139.
78.周先碗,胡晓倩.生物化学仪器分析与实验技术[M].北京：化学工业出版社,2002：90-92.
79. Srivastava PK. Purification of heat shock protein-peptide complexes for use in vaccination against cancers and intracellular pathogens [J]. Methods,1997,12: 165-171.
80. Arnold D, Faath S, Rammensee H, et al. Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96 [J]. J Exp Med,1995,82:885-889.
81. Bethke K, Staib F, Distler M, et al. Different efficiency of heat shock proteins (HSP) to activate human monocytes and dendritic cells:superiority of HSP60 [J]. J Immunol,2002,169:6141-6148.
82. Menoret A, Chandawarkar R. Heat-shock protein-based anticancer immunotherapy:an idea whose time has come [J]. Semin Oncol,1998,25:654-660.
83. Sastry S, Linderoth N. Molecular mechanisms of peptide loading by the tumor rejection antigen/heat shock chaperone gp96(GRP94) [J]. J Biol Chem,1999, 274:12023-12035.
84. Csermely P, Schnaider T, Soti C, et al. The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review [J]. Pharmacol Ther,1998,79:129-168.
85. Asea A, Rehli M, Kabingu E, et al. Novel signal transduction pathway utilized by extracellular HSP70:role of toll-like receptor(TLR) 2 and TLR4 [J]. J Biol Chem,2002,277(17):15028-15034.
86. Janetzki S, Palla D, Rosenhauer V, et al.Immunization of cancer patients with autologous cancer-derived heat shock protein gp96 preparations:a pilot study [J]. Int J Cancer.2000,88(2):232-238.
87. Mazzaferro V, Coppa J, Carrabba MG, et al. Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer [J]. Clin Cancer Res.2003,9(9):3235-3245.
88. Rivoltini L, Castelli C, Carrabba M, et al. Human tumor-derived heat shock protein 96 mediates in vitro activation and in vivo expansion of melanoma-and colon carcinoma-specific T cells [J]., J Immunol.2003,171(7):3467-3474.
89. Fleischer K, Schmidt B, Kastenmtiller W, et al. Melanoma-reactive class I-restricted cytotoxic T cell clones are stimulated by dendritic cells loaded with synthetic peptides, but fail to respond to dendritic cells pulsed with melanoma-derived heat shock proteins in vitro [J]. J Immunol.2004,172(1): 162-169.
90. Menoret A, Chandawarkar RY, Srivastava PK. Natural autoantibodies against heat-shock proteins hsp70 and gp96:implications for immunotherapy using heat-shock proteins [J]. Immunology,2000,101(3):364-370.
91. Arnold-Schild D, Kleist C, Welschof M, et al. One-step single-chain Fv recombinant antibody-based purification of gp96 for vaccine development [J]. Cancer Res,2000,60(15):4175-4178.
92. Berwin B, Reed RC, Nicchitta CV. Virally induced lytic cell death elicits the release of immunogenic GRP94/gp96 [J].J Biol Chem,2001,276(24):21083-21088.
93. Belli F, Testori A, Rivoltini L, et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings [J]. J Clin Oncol.2002,20(20):4169-4180.
94. Makki A, Weidt G, Blachere NE, et al. Immunization against a dominant tumor antigen abrogates immunogenicity of the tumor [J].Cancer Immun.2002,16,2-4.
95. Stebbing J, Bower M, Srivastava P. Kaposi's sarcoma as a model for cancer immunotherapy [J]. Trends Mol Med.2004,10(4):187-193.
96. Srivastava P. Heat shock proteins and immune response:methods to madness [J]. Methods.2004,32(1):1-2.
97. Maki RG, Livingston PO, Lewis JJ, et al. A phase I pilot study of autologous heat shock protein vaccine HSPPC-96 in patients with resected pancreatic adenocarcinoma [J]. Dig Dis Sci.2007,52(8):1964-1972.
98. Oki Y, McLaughlin P, Fayad LE, et al. Experience with heat shock protein-peptide complex 96 vaccine therapy in patients with indolent non-Hodgkin lymphoma [J]. Cancer.2007,109(1):77-83.
99. Yedavelli SP, Guo L, Daou ME, et al. Preventive and therapeutic effect of tumor derived heat shock protein, gp96, in an experimental prostate cancer model [J]. Int J Mol Med.1999,4(3):243-248.
100. Przepiorka D, Srivastava PKHeat shock protein--peptide complexes as immunotherapy for human cancer [J]. Mol Med Today.1998,4(11):478-484.
101. Srivastava PK, Menoret A, Basu S, et al. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world [J]. Immunity.1998, 8(6):657-665.
102. Chandawarkar RY, Wagh MS, Srivastava PK. The dual nature of specific immunological activity of tumor-derived gp96 preparations [J]. J Exp Med.1999, 189(9):1437-1442.
103.Srivastava PK, Kozak CA, Old LJ. Chromosomal assignment of the gene encoding the mouse tumor rejection antigen gp96 [J]. Immunogenetics.1988, 28(3):205-207.
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